Figure 2.

The effect of p62 on Nrf2 and NF-κB signaling.

Upon exposure to oxidative stress, p62 is phosphorylated at Serine residues 403 and 349, and binds to the Nrf2-inhibitory protein Keap1, shuttling it to the autophagosome for degradation. Nrf2 can then enter the nucleus and promote transcription of ARE-genes, including p62, which can also downregulate NF-κB signaling. Keap1: Kelch-like receptor protein 1; NF- κB: nuclear factor-kappa B; Nrf2: nuclear-erythroid factor-2; TRAF6: tumor necrosis factor receptor associated factor 6; ZZ: zinc finger.